The role of nitric oxide in the control of plasma glucose concentration in spontaneously hypertensive rats

Glucose homeostasis was studied in the spontaneously hypertensive rat (SHR). The fasting plasma glucose levels were similar in the SHR and normotensive Wistar-Kyoto (WKY) rat (102.7 ± 2.4 vs. 107.4 ± 4.2 mg/dl, P > 0.01). One hour after glucose challenge, the plasma glucose level was slightly but insignificantly increased in both SHR and WKY rat (117 ± 2.5 vs. 114.3 ± 3.2 mg/dl, P > 0.01). After N(G)-nitro-L-arginine methyl ester (L-NAME) 20 mg/kg per day was administered intraperitoneally (i.p.) for 4 days, the plasma glucose level was significantly increased in the rats (SHR 167.3 ± 4.9; WKY rat 136.0 ± 4.8 mg/dl); the increase was significantly more pronounced in the SHR. The fasting insulin levels were similar in the SHR and WKY rats (2.3 ± 0.4 vs. 2.0 ± 0.3 ng/ml, P > 0.01). One hour after glucose challenge the insulin level was significantly increased in the WKY rat (4.8 ± 0.7 ng/ml) but not in the SHR (2.2 ± 0.4 ng/ml). With L-NAME treatment, plasma insulin increase was noted in the WKY rat but not SHR (4.6 ± 0.6 vs. 2.6 ± 0.4 ng/ml, n = 8, P < 0.01). One hour after insulin 1 IU/kg was injected intramuscularly (i.m.) the plasma glucose level was significantly decreased in both the SHR (from 115.0 ± 6.5 to 48.6 ± 3.6 mg/dl, n = 8) and WKY rat (from 108.3 ± 3.8 to 52.6 ± 4.2 mg/dl, n = 8). No significant difference was noted between the decrease of the two groups (P > 0.01). The present findings suggested that NO plays a role in the glucose homeostasis of rats. NO-synthase blockade resulted in an increase of plasma glucose level. The SHR maintains normal glucose level and tolerance in spite of a defective insulin release response. This is probably due the compensatory effect of a more prominent NO-dependent glucose homeostatic function.